Citations

Purpose The purpose of this study was to assess the feasibility of a nurse-driven effort to improve hyperglycemia management in the intensive care unit (ICU) setting. Methods The setting was the ICU of a large urban hospital. The program was composed of 3 components: nurses as leaders, a clinical pathway to identify patients in need of hyperglycemia therapy, and implementation of a redesigned insulin infusion algorithm (the Columnar Insulin Dosing Chart). Time to reach a target glucose range of 80 to 110 mg/dL (4.4-6.1 mmol/L) was evaluated. Results One hundred sixteen ICU nurses were trained in the project. The Columnar Insulin Dosing Chart was applied to 20 patients. The average time required to reach the target blood glucose range was 12.8 hours. Below-target blood glucose levels were 6.9% of all blood glucose levels recorded, but only 0.9% were below 60 mg/dL (3.3 mmol/L). There was no sustained hypoglycemia, and no persistent clinical findings attributable to hypoglycemia were noted. Barriers to implementing the project included an increased nursing workload, the need for more finger-stick blood glucose monitors, and the need to acquire new finger-lancing devices that allowed for shallower skin puncture and increased patient comfort. Conclusions Tighter glycemic control goals can be attained in a busy ICU by a nurse-led team using a pathway for identifying and treating hyperglycemia, clear decision support tools, and adequate nurse education. The novel chart based insulin infusion algorithm chosen as the standard for this pilot was an effective tool for reducing the blood glucose to target range with no clinically significant hypoglycemia.

The decrease in estrogen levels that follows the onset of menopause results in rapid bone loss and osteoporosis. The major effect of estrogen deficiency on bone metabolism is an increase in the rate of bone resorption, but the precise mechanism by which this occurs remains unresolved. A recently developed technique for the isolation of avian osteoclasts has been modified to obtain highly purified multinucleated cells from human giant cell tumors. These osteoclast-like cells have been examined for evidence of estrogen receptors (ERs) and responses to 17 beta-estradiol (17 beta-E2). Analysis of giant-cell RNA demonstrated expression of ER mRNA. Furthermore, immunoblot analysis revealed that the giant cells contained a 66-kDa protein that was recognized by a monoclonal antibody specific for the human ER. When isolated multinucleated cells were cultured on slices of bone, there was a dose-dependent decrease in resorption in response to treatment detectable at 10 pM 17 beta-E2. Treatment with 10 nM 17 alpha-estradiol or vehicle (control) did not inhibit resorption. Moreover, the multinucleated cells isolated from these tumors had decreased mRNA levels for cathepsin B, cathepsin D, and tartrate-resistant acid phosphatase (TRAP) as well as secreted cathepsin B and TRAP enzyme activity in response to treatment with 10 nM 17 beta-E2. In contrast to these data, no change in gene expression was detected in mononuclear cells from these tumors in response to 17 beta-E2 treatment. These data support the proposition that human osteoclasts are target cells for estrogen and that estrogen can inhibit bone resorption by human osteoclasts.

Although in vivo effects of 17 beta-estradiol (estrogen) on bone turnover have been shown to occur mainly through influences on osteoclast-mediated bone resorption, the mechanism by which estrogen reduces bone resorption is unclear. To approach this question, we have examined authentic osteoclasts for evidence of a direct osteoclast response to estrogen in vitro. Highly purified (greater than (90%) viable avian osteoclasts from birds maintained on a low calcium diet were obtained using an osteoclast-specific monoclonal antibody coupled to magnetic beads. Isolated cells were either analyzed directly for estrogen receptor (ER) levels or cultured to assess the biological effects of estrogen. Northern blot analysis revealed a 5.2-kilobase mRNA that hybridized with a cDNA to human ER mRNA in the osteoclasts. An anti-human ER antibody recognized proteins of 66 kDa and 140 kDa in osteoclast extracts by Western blot analysis. The 66-kDa size is in close agreement with the reported size of the human ER. Nuclear binding of estrogen to intact viable osteoclasts was steroid-specific and saturable, with 5662 +/- 1420 molecules bound per nucleus (mean +/- SEM). In vitro estrogen responses in osteoclasts included a dose-dependent decrease in resorption as well as an increase in nuclear protooncogene mRNA levels. These observations indicate that osteoclasts are capable of directly responding to estrogen in vivo.

The sex steroids, androgens and estrogens, are major regulators of bone metabolism. However, whether these hormones act on bone cells through direct or indirect mechanisms has remained unclear. A nuclear binding assay recently used to demonstrate estrogen receptors in bone [Eriksen, E.F., Colvard, D.S., Berg, N.J., Graham, M.L., Mann, K.G., Spelsberg, T.C. & Riggs, B.L. (1988) Science 241, 84-86] was used to identify specific nuclear binding of a tritiated synthetic androgen, [3H]R1881 (methyltrienolone), in 21 of 25 (84%) human osteoblast-like cell strains and a concentration of bound steroid receptors of 821 +/- 140 (mean +/- SEM) molecules per cell nucleus. Binding was saturable and steroid-specific. Androgen receptor gene expression in osteoblasts was confirmed by RNA blot analysis. Relative concentrations of androgen and estrogen receptors were compared by measuring specific nuclear estrogen binding. Nuclear binding of [3H]estradiol was observed in 27 of 30 (90%) cell strains; the concentration of bound estradiol receptor was 1537 +/- 221 molecules per cell nucleus. The concentrations of nuclear binding sites were similar in males and females for both [3H]R1881 and [3H]estradiol. We conclude that both androgens and estrogens act directly on human bone cells through their respective receptor-mediated mechanisms.

Abstract The NOF cost-effectiveness model, based on clinical risk factors and femoral neck aBMD, predicted overall fracture risk in a cohort of postmenopausal women followed for up to 22 years. Introduction: To assess the ability of a statistical model to predict long-term fracture risk for a population of postmenopausal women, we compared observed fractures to those predicted by the National Osteoporosis Foundation's (NOF) cost-effectiveness model. Materials and Methods: In this population-based study, 393 postmenopausal Rochester, MN, women had baseline measurements of femoral neck areal BMD (aBMD) and assessment of the clinical risk factors (personal fracture history, family history of osteoporotic fracture, low body weight, and smoking status) that were included in the NOF model. They were then followed prospectively for up to 22 years. Fractures were ascertained by periodic interview and review of community medical records. Standardized incidence ratios (SIRs) compared observed fractures to predicted numbers. Results: During 4782 person-years of follow-up, 212 women experienced 503 fractures, two-thirds of which were caused by moderate trauma. When undiagnosed (incidentally noted) vertebral and rib fractures were excluded, there was general concordance between observed and predicted fractures of the hip (SIR, 0.78; 95% CI, 0.56-1.01), distal forearm (SIR, 1.22; 95% CI, 0.86-1.68), spine (SIR, 0.76; 95% CI, 0.50-1.11), and all other sites combined (SIR, 1.18; 95% CI, 0.97-1.42). Fracture prediction by the NOF model was about as good after 10 years as it was earlier during follow-up. Conclusions: This study validates the ability of a statistical model based on femoral neck aBMD and common clinical risk factors to predict the actual occurrence of fractures in a cohort of postmenopausal white women.

Abstract Osteoporosis is widely viewed as a major public health concern, but the exact magnitude of the problem is uncertain and likely to depend on how the condition is defined. Noninvasive bone mineral measurements can be used to define a state of heightened fracture risk (osteopenia), or the ultimate clinical manifestation of fracture can be assessed (established osteoporosis). If bone mineral measurements more than 2 standard deviations below the mean of young normal women represent osteopenia, then 45% of white women aged 50 years and over have the condition at one or more sites in the hip, spine, or forearm on the basis of population-based data from Rochester, Minnesota. A smaller proportion is affected at each specific skeletal site: 32% have bone mineral values this low in the lumbar spine, 29% in either of two regions in the proximal femur, and 26% in the midradius. Although this overall estimate is substantial, some other serious chronic diseases are almost as common. More importantly, low bone mass is associated with adverse health outcomes, especially fractures. The lifetime risk of any fracture of the hip, spine, or distal forearm is almost 40% in white women and 13% in white men from age 50 years onward. If the enormous costs associated with these fractures are to be reduced, increased attention must be given to the design and implementation of control programs directed at this major health problem.